Although many theories of substance abuse emphasize the role of negative reinforcement processes in drug dependence, our understanding of the effects of drugs of abuse on behavior maintained by negative reinforcement remains incomplete. One reason is that techniques that permit the study of the actions of drugs on negatively-reinforced behavior are quite limited. The proposed research will elaborate on a procedure developed in our laboratory that permits the study of behavior maintained by two concurrently available sources of negative reinforcement in rats: avoidance and timeout from avoidance. The timeout from avoidance procedure is of particular value in that timeout can be programmed using the same schedule arrangements as positive reinforcers, thus permitting comparisons between drug effects with the two types of reinforcers. In previous research using this technique, unique and opposite effects were produced by drugs of abuse morphine and amphetamine. The proposed studies will evaluate the generality of these effects by determining whether the effects of morphine are shared by other opioid compounds such as fentanyl, methadone, buprenorphine, and the specific kappa agonist U50,488. Related studies will assess whether the effects of amphetamine are shared by other stimulant drugs such as cocaine, and by drugs that affect specific receptor sites in the dopaminergic systems such as SCH23390, SKF38393, raclopride, and quinpirole. Further proposed research will help to determine the proper interpretation of the actions of drugs of abuse on timeout from avoidance by analyzing the extent to which morphine and amphetamine effects are due to altered magnitude or efficacy of negative reinforcement.